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1-Chloro-2,2,2-trifluoroethyl radical: Formation from halothane by human cytochrome P-450 in reconstituted vesicles and binding to phospholipids.
Trudell JR; Bösterling B; Trevor A
Biochem Biophys Res Commun 1981 Sep; 102(1):372-377
Anaerobic metabolism of halothane (151677) was studied in vesicles composed of cytochrome-P-450, NADPH cytochrome-P-450-reductase, and cytochrome-b5 reconstituted in a mixture of dioleoylphosphatidylcholine and egg phosphatidylethanolamine. It was anticipated that free radicals of carbene metabolites formed from halothane would add to the single 9,10 double bond of the identical oleic-acid chains in dioleoylphosphatidylcholine. Significant covalent binding of radioactive metabolites to phospholipids was noted following incubation of reconstituted vesicles with carbon-14 labeled halothane under argon. A single peak of radioactivity was eluted at 23 minutes under conditions where methyl-oleate eluted at 26 minutes following transesterification of the dioleoylphosphatidylcholine fraction and separation of the methyl esters on a C18 reverse phase column. The findings were consistent with the addition of a CF3CHCl radical to the double bond of oleic-acid followed by abstraction of a hydrogen radical from a neighboring donor. Formation of a trifluoroethyl- carbene on cytochrome-P-450 following anaerobic incubation with halothane has been postulated. It is likely that a cyclopropane product resulting from addition of 2,2,2-trifluoroethyl-carbene to the 9,10 double bond of oleic-acid would be stable under the conditions of extraction and transesterification employed in this study. But, such an addition product was not found, suggesting that either the cytochrome P-450-carbene complex was so stable that it did not dissociate once formed, that the lifetime of the carbene was too short to diffuse to a double bond, or that the peak in absorption at 470 nanometers was not due to a carbene complex.
NIOSH-Publication; NIOSH-Grant; Grants-other; Metabolic-study; Anesthetics; Halogenated-hydrocarbons
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
Issue of Publication
Other Occupational Concerns; Grants-other
Biochemical and Biophysical Research Communications
Stanford University, Stanford, California
Page last reviewed: October 9, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division